title: Combination gefitinib and methotrexate compared with methotrexate alone to treat ectopic pregnancy.
abstract: OBJECTIVE
  To determine the safety, tolerability, and efficacy of combination gefitinib and methotrexate to treat ectopic pregnancy.
  
  
  METHODS
  We performed a phase I, single-arm (nonrandomized), open-label study. Twelve women with ectopic pregnancies were administered methotrexate (50 mg/m, intramuscular) and 250 mg oral gefitinib in a dose-escalation protocol: one dose (day 1) n=3; three doses (days 1-3) n=3; seven doses (days 1-7) n=6. Efficacy was examined by comparing human chorionic gonadotrophin (hCG) decline and time to resolution with historic controls administered methotrexate only.
  
  
  RESULTS
  Common side effects were transient acneiform rash in 67% (8/12) and diarrhea in 42% (5/12) of participants. There was no clinical or biochemical evidence of serious pulmonary, renal, hepatic, or hematologic toxicity. Of six participants with a pretreatment serum hCG level between 1,000 and 3,000 international units/L, hCG levels declined significantly faster than in the control group. Median serum hCG levels by day 7 after treatment were less than one fifth of levels observed among 71 historic controls treated with methotrexate alone (median [interquartile range] hCG in participants 261 [55-1,445] international units/L compared with controls 1,426 [940-2,573]; P=.008). Median time for the ectopic pregnancies to resolve with combination therapy was 34% shorter compared with methotrexate alone (21 days compared with 32 days; P=.018).
  
  
  CONCLUSIONS
  Combination gefitinib and methotrexate has potential as a treatment for ectopic pregnancy but is commonly associated with minor side effects such as transient rash and diarrhea. The treatment requires validation of safety and efficacy in a larger trial.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry, www.anzctr.org, AC'TRN12610000684022.
  
  
  METHODS
  : II.
authors.affiliation: Translational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, and the Ritchie Centre and the Centre for Cancer Research, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia; and the MRC Centre for Reproductive Health, the Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Monika M
authors.initials: MM
authors.lastname: Skubisz
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
authors.forename: Terrance G
authors.initials: TG
authors.lastname: Johns
authors.forename: Ulrika W
authors.initials: UW
authors.lastname: Nilsson
authors.forename: W Colin
authors.initials: WC
authors.lastname: Duncan
authors.forename: Euan M
authors.initials: EM
authors.lastname: Wallace
authors.forename: Hilary O D
authors.initials: HOD
authors.lastname: Critchley
authors.forename: Stephen
authors.initials: S
authors.lastname: Tong
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000627:therapeutic use*; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007273:Injections, Intramuscular; D008727:Methotrexate / Q000627:therapeutic use*; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000188:drug therapy*; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib; D008727:Methotrexate